Gelatin

Code: c74
Source material: Gelatin of bovine origin
Gelatin is used in plasma substitutes and in vaccines.

Allergen Exposure

Gelatin is widely used in foods, drugs and devices. It is used in plasma substitutes and in vaccines. It is also used in photographic emulsions, glues, matches, cosmetics and much more.

Potential Cross-Reactivity

Cross-reactivity between gelatin of different animal origin exists. IgE to bovine and porcine gelatin was tested in 26 children with systemic immediate reactions to vaccines. Two had no IgE to either kind of gelatin, 20 had almost the same level to both, and 4 had higher levels to bovine gelatin. The cross-reactivity was further demonstrated with ELISA inhibition (6).

Clinical Experience

Immediate IgE-mediated reactions have been reported, as well as systemic reactions and anaphylaxis. Allergic reactions after gelatin-containing live vaccines are increasingly reported (1-5, 9). Reports of plasma substitute reactions also express concern for using gelatin-containing products (4). Allergic reactions to fruit-gums (6, 7, 9), marshmallows (8) and "gelatin of any kind" (5) have been reported as well.
 
Review
Gelatin is prepared by the hydrolysis of collagen from various animal sources, e.g. bovine and porcine hide and bones.
Collagen in the form of intestines from sheep and cattle has been the prime source of strings for musical instruments since the Middle Ages, and subsequently in the production of suture material. Gelatin is widely used in foods, drugs and devices. It is used in plasma substitutes and in vaccines. It is also used in photographic emulsions, glues, matches, cosmetics and much more. Immediate IgE-mediated reactions have been reported, as well as systemic reactions and anaphylaxis.

Vaccines: Allergic reactions after gelatin-containing live vaccines are increasingly reported in Japan. Two types of adverse reactions are suggested, cutaneous and respiratory symptoms would be IgE-mediated, whereas cardiovascular symptoms would not. This theory was tried and confirmed by gelatin IgE testing with Pharmacia CAP System in six children from each of the two categories (1).

In another study, adverse reactions to gelatin-containing vaccines were categorized as immediate and non-immediate. Six patients with immediate reactions were gelatin positive with Pharmacia CAP System, and 21 patients with non-immediate reactions were negative.

In a retrospective study from 1994 - 1997 in Japan, 336 patient reports of adverse reactions after gelatin containing vaccinations were studied. IgE to gelatin was tested in the 206 serum samples that were available, and detected in 25/27 patients with anaphylaxis, 27/48 with urticaria and 8/90 with generalized eruptions (2). In another study, specific IgE to gelatin was measured with Pharmacia CAP System in 64 of 525 allergic children, and 17 were positive. Nine out of 11 children with both IgE and IgG to gelatin reported adverse reactions to gelatin-containing products. Five of them had episodes of anaphylaxis, two to vaccines and three to fruit-gums (9).

More reports support the above findings (3-5).
 
Plasma substitutes: Reports of plasma substitute reactions also express concern for using gelatin-containing products. In France, a prospective questionnaire was distributed to 49 clinics from June 1991 to October 1992. All patients receiving plasma substitute, with or without reaction, were recorded. A total of 19.593 patients were registered, of which 48% had been given gelatin-containing substitutes. In total, 43 reactions were reported, and for gelatin-containing substitutes, the incidence of adverse events was 0.345% (4).
 
Ingested gelatin: Allergy to foods containing gelatin should be considered after reactions to such foods.
This also holds true for reactions to candies, which are often coloured with azo-dyes, and where the blame for intolerances has up to now been placed upon these dyes. Allergic reactions to fruit-gums (6, 7, 9), marshmallows (8) and "gelatin of any kind" (5) have been reported.

Devices: Two patients were reported to have IgE-mediated allergic reactions to bovine collagen, corneal shields and catgut suture material, after ophthalmic surgery. One of them also reacted to collagen in the form of gelatin-containing food (8).
 
Cross-reactivity between gelatin of different animal origin exists. IgE to bovine and porcine gelatin was tested in 26 children with systemic immediate reactions to vaccines. Two had no IgE to either kind of gelatin, 20 had almost the same level to both, and 4 had higher levels to bovine gelatin. The cross-reactivity was further demonstrated with ELISA inhibition (6).

 

References

  1. Sakaguchi M, Inouye S. Two patterns of systemic immediate-type reactions to Japanese encephalitis vaccines. Vaccine 1998;16(1):68-9.
  2. Nakayama T, Aizawa C, Kuno-Sakai H. A clinical analysis of gelatin allergy and determination of its causal relationship to the previous administration of gelatin-containing acellular pertussis vaccine combined with diphtheria and tetanus toxoids [see comments]. J Allergy Clin Immunol 1999;103(2 Pt 1):321-5.
  3. Singer S, Johnson CE, Mohr R, Holowecky C. Urticaria following varicella vaccine associated with gelatin allergy. Vaccine 1999;17(4):327-9.
  4. Laxenaire MC, Charpentier C, Feldman L. [Anaphylactoid reactions to colloid plasma substitutes: incidence, risk factors, mechanisms. A French multicenter prospective study (see comments)]. Ann Fr Anesth Reanim 1994;13(3):301-10.
  5. Kelso JM, Jones RT, Yunginger JW. Anaphylaxis to measles, mumps, and rubella vaccine mediated by IgE to gelatin. J Allergy Clin Immunol 1993;91(4):867-72.
  6. Sakaguchi M, Nakayama T, Inouye S. Food allergy to gelatin in children with systemic immediate-type reactions, including anaphylaxis, to vaccines. J Allergy Clin Immunol 1996;98(6 Pt 1):1058-61.
  7. Wahl R, Kleinhans D. IgE-mediated allergic reactions to fruit gums and investigation of cross-reactivity between gelatine and modified gelatine-containing products. Clin Exp Allergy 1989;19(1):77-80.
  8. Mullins RJ, Richards C, Walker T. Allergic reactions to oral, surgical and topical bovine collagen. Anaphylactic risk for surgeons. Aust N Z J Ophthalmol 1996;24(3):257-60.
  9. Kawahara H, Tanaka K, Iikura Y, Akasawa A, Saito H. The incidence of gelatin allergy among atopic children in Japan. J Allergy Clin Immunol 1998;101(1):2

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.